Proton spectroscopic imaging (Dixon method) of the liver: clinical utility

The contribution of proton spectroscopic (PS) imaging to magnetic resonance (MR) imaging of the liver was assessed at 0.5 T in 55 patients with known or suspected hepatic malignancy. PS images were compared subjectively with T1- and T2-weighted spin-echo (SE) images for hepatic lesion detection and conspicuity. For hepatic metastases (n = 27), PS images were equal to T1-weighted images in lesion detection in 17 patients but showed fewer lesions in five patients and false-negative results in two. When compared with T2-weighted images, PS images depicted more lesions in six patients, an equal number of lesions in 18, and fewer lesions in two. Hepatomas (n = 8) were detected with each sequence in all patients. Hepatomas were often more conspicuous on PS images than on T2-weighted images; they were of equal conspicuity on PS and T1-weighted images in most cases. Whereas fatty infiltration (n = 16) appeared on PS images as areas of low signal intensity similar to that of paraspinal muscle, it produced no detectable abnormality on either T1- or T2-weighted images. PS imaging is inferior to T1-weighted SE imaging in the detection of hepatic metastases. The major role of PS imaging at intermediate field strength is to differentiate focal fatty infiltration from hepatic metastases.     

Application of phosphoramidate ProTide technology significantly improves antiviral potency of carbocyclic adenosine derivatives

We report the application of phosphoramidate pronucleotide (ProTide) technology to the antiviral agent carbocyclic L-d4A (L-Cd4A). The phenyl methyl alaninyl parent ProTide of L-Cd4A was prepared by Grignard-mediated phosphorochloridate reaction and resulted in a compound with significantly improved anti-HIV (2600-fold) and HBV activity. We describe modifications of the aryl, ester, and amino acid regions of the ProTide and how these changes affect antiviral activity and metabolic stability. Separate and distinct SARs were noted for HIV and HBV. Additionally, ProTides were prepared from the D-nucleoside D-Cd4A and the dideoxy analogues L-CddA and D-CddA. These compounds showed more modest potency improvements over the parent drug. In conclusion, the ProTide approach is highly successful when applied to L-Cd4A with potency improvements in vitro as high as 9000-fold against HIV. With a view to preclinical candidate selection we carried out metabolic stability studies using cynomolgus monkey liver and intestinal S9 fractions.     

Treatment of intracerebral arteriovenous malformations with isobutyl 2- cyanoacrylate: initial clinical experience

From November 1976 to September 1979, 46 patients with intracranial arteriovenous malformations or fistulas participated in a clinical study using isobutyl 2-cyanoacrylate (IBCA), with tantalum, for palliative or preoperative occlusion of the blood supply to the abnormalities. Although failure to obtain satisfactory position of a functioning microcatheter precluded deposition of IBCA 10 times, a total of 51 of a possible 62 feeding vessels were occluded with the tantalum-impregnated glue. The technique, results, and complications are discussed in light of the clinical follow-up, which varied from 12 to 48 months.     

Biochemical and molecular analysis of carboxylesterase-mediated hydrolysis of cocaine and heroin

Background and purpose:

Carboxylesterases (CEs) metabolize a wide range of xenobiotic substrates including heroin, cocaine, meperidine and the anticancer agent CPT-11. In this study, we have purified to homogeneity human liver and intestinal CEs and compared their ability with hydrolyse heroin, cocaine and CPT-11.

Experimental approach:

The hydrolysis of heroin and cocaine by recombinant human CEs was evaluated and the kinetic parameters determined. In addition, microsomal samples prepared from these tissues were subjected to chromatographic separation, and substrate hydrolysis and amounts of different CEs were determined.

Key results:

In contrast to previous reports, cocaine was not hydrolysed by the human liver CE, hCE1 (CES1), either as highly active recombinant protein or as CEs isolated from human liver or intestinal extracts. These results correlated well with computer-assisted molecular modelling studies that suggested that hydrolysis of cocaine by hCE1 (CES1), would be unlikely to occur. However, cocaine, heroin and CPT-11 were all substrates for the intestinal CE, hiCE (CES2), as determined using both the recombinant protein and the tissue fractions. Again, these data were in agreement with the modelling results.

Conclusions and implications:

These results indicate that the human liver CE is unlikely to play a role in the metabolism of cocaine and that hydrolysis of this substrate by this class of enzymes is via the human intestinal protein hiCE (CES2). In addition, because no enzyme inhibition is observed at high cocaine concentrations, potentially this route of hydrolysis is important in individuals who overdose on this agent.     

龙血竭胶囊治疗软组织挫伤230例

1 临床资料软组织挫伤460(男300,女160)例,年龄5～72(平均38)岁,面部伤86例,躯干伤98例,四肢伤200例,躯干合并四肢伤76例,均为12 h内收治病例. 实验组(n=230)给于龙血竭胶囊(龙血竭胶囊是由植物防卫素和龙血竭皂甙组成)口服,3次/d,每次1.2 g;对照组(n=230)给于跌打丸口服,2次/d,每次1丸,疗程均为6 d. 实验组总有效率为96.5%,对照组为83.5%,两组间有显著差别(P<0.01). 实验组用药后3和6 d血糖值均较对照组有明显下降(P<0.01). 实验组与对照组用药后总抗氧化能力(TAO, kU/L)均升高(12.5±0.08→42.5±0.03, 12.6±0.05→32.9±0.04),但实验组升高明显(P<0.01).     

Growth monitoring: testing the new guidelines

OBJECTIVE: To assess the impact of recent guidelines from the UK joint working party of child health surveillance recommending that all children be measured at age 5 and again between 7 and 9 years of age to determine how many normal school age children are likely to be referred for specialist assessment. METHODS: The longitudinal data of 486 children measured by school nurses in a community setting were examined and compared with measurements made in a research setting by a single, skilled observer. MAIN OUTCOME MEASURES: Number of children identified as having abnormal stature (< 0.4th or > 99.6th centile) and abnormal growth rate height standard deviation score (HSDS) change > 0.67). RESULTS: The community survey identified seven (1.4%) children as having abnormal stature (four short, three tall), 11 (2.3%) were identified as "slow growing", and nine (1.9%) increased their HSDS by more than 0.67. These results were comparable to data collected in ideal research conditions. CONCLUSIONS: Following the recommendations would not result in an excess number of inappropriate referrals. However, this study highlights several unresolved issues such as interobserver variability and time interval between measurements. A large scale prospective study should be considered to establish realistic and cost-effective criteria before implementation of a national screening programme.